Aspartate aminotransferase: investigation of the active sites.
An investigation of the crystal structure of cytosolic pig-heart aspartate aminotransferase (AAT, E.C.2.6.1.1) was carried out to determine the structural requirements for ligand recognition by the active site. Structural differences were observed between the two active sites of the AAT dimer. The natural ligand, L-aspartate, was docked into both active sites using various methods. However, due to structural differences, the ligand was able to form all the necessary interactions for initial binding in only one of the active sites. The program GRID (P.J. Goodford, J. Med. Chem. 1985, 28, 849-857) was used to predict favorable binding sites for the functional groups of the aspartate ligand. These binding sites corresponded to the position of the docked aspartate ligand, indicating that substrate recognition takes place before any major conformational changes occur within the enzyme.
Nero
T L
TL
School of Pharmaceutical Chemistry, Victorian College of Pharmacy Ltd, Parkville, Australia.
Wong
M G
MG
Oliver
S W
SW
Iskander
M N
MN
Andrews
P R
PR
D000818:Animals; D001219:Aspartate Aminotransferases / Q000737:chemistry* / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D001665:Binding Sites; D002645:Chickens; D003196:Computer Graphics; D003600:Cytosol / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D011487:Protein Conformation; D013552:Swine
D001224:Aspartic Acid; D001219:Aspartate Aminotransferases